A novel trend is rapidly emerging in the use of microneedles, which are a miniaturized replica of hypodermic needles with length-scales of hundreds of micrometers, aimed at the transdermal biosensing of analytes of clinical interest, e.g., glucose, biomarkers, and others. Transdermal biosensing via microneedles offers remarkable opportunities for moving biosensing technologies and biochips from research laboratories to real-field applications, and envisages easy-to-use point-of-care microdevices with pain-free, minimally invasive, and minimal-training features that are very attractive for both developed and emerging countries. In addition to this, microneedles for transdermal biosensing offer a unique possibility for the development of biochips provided with end-effectors for their interaction with the biological system under investigation. Direct and efficient collection of the biological sample to be analyzed will then become feasible in situ at the same length-scale of the other biochip components by minimally trained personnel and in a minimally invasive fashion. This would eliminate the need for blood extraction using hypodermic needles and reduce, in turn, related problems, such as patient infections, sample contaminations, analysis artifacts, etc. The aim here is to provide a thorough and critical analysis of state-of-the-art developments in this novel research trend, and to bridge the gap between microneedles and biosensors.

Low-cost piezoresistive strain/pressure sensors with large working range, at the same time able to reliably detect ultralow strain (≤0.1%) and pressure (≤1 Pa), are one of the challenges that have still to be overcome for flexible piezoresistive materials toward personalized health-monitoring applications. In this work, we report on unprecedented, simultaneous detection of ultrasmall strain (0.1%, i.e., 10 μm displacement over 10 mm) and subtle pressure (20 Pa, i.e., a force of only 2 mN over an area of 1 cm) in compression mode, coupled with a large working range (i.e., up to 60% for strain-6 mm in displacement-and 50 kPa for pressure) using piezoresistive, flexible three-dimensional (3D) macroporous polydimethylsiloxane (pPDMS) foams decorated with pristine multiwalled carbon nanotubes (CNTs). pPDMS/CNT foams with pore size up to 500 μm (i.e., twice the size of those of commonly used foams, at least) and porosity of 77%, decorated with a nanostructured surface network of CNTs at densities ranging from 7.5 to 37 mg/cm are prepared using a low-cost and scalable process, through replica molding of sacrificial sugar templates and subsequent drop-casting of CNT ink. A thorough characterization shows that piezoresistive properties of the foams can be finely tuned by controlling the CNT density and reach an optimum at a CNT density of 25 mg/cm, for which a maximum change of the material resistivity (e.g., ρ/ρ = 4 at 50% strain) is achieved under compression. Further static and dynamic characterization of the pPDMS/CNT foams with 25 mg/cm of CNTs highlights that detection limits for strain and pressure are 0.03% (3 μm displacement over 10 mm) and 6 Pa (0.6 mN over an area of 1 cm), respectively; moreover, good stability and limited hysteresis are apparent by cycling the foams with 255 compression-release cycles over the strain range of 0-60%, at different strain rates up to 10 mm/min. Our results on piezoresistive, flexible pPDMS/CNT foams pave the way toward breakthrough applications for personalized health care, though not limited to these, which have not been fully addressed to date with flexible strain/stress sensors.

In-field analysis (e.g., clinical and diagnostics) using nanostructured porous silicon (PSi) for label-free optical biosensing has been hindered so far by insufficient sensitivity of PSi biosensors. Here we report on a label-free PSi interferometric aptasensor able to specifically detect tumor necrosis factor alpha (TNFα, a protein biomarker of inflammation and sepsis) at concentration down to 3.0 nM with signal-to-noise ratio (S/N) of 10.6 and detection limit (DL) of 200 pM. This represents a 10 000-fold improvement with respect to direct (i.e., nonamplified) label-free PSi biosensors and pushes PSi biosensors close to the most sensitive optical and label-free transduction techniques, e.g., surface plasmon resonance (SPR) for which a lowest DL of 100 pM in aptasensing has been reported. A factor 1000 in improvement is achieved by introducing a novel signal-processing technique for the optical readout of PSi interferometers, namely, interferogram average over wavelength (IAW) reflectance spectroscopy. The IAW reflectance spectroscopy is shown to significantly improve both sensitivity and reliability of PSi biosensors with respect to commonly used fast Fourier transform (FFT) reflectance spectroscopy. A further factor 10 is achieved by enabling preparation of PSi interferometers with enlarged pore sizes (up to a 3× increase in diameter) at constant current density (i.e., constant porosity and, in turn, constant refractive index). This method is in contrast to standard PSi preparation where pore size is increased by increasing etching current density (i.e., porosity), and allows tackling mass-limited diffusion of biomolecules into the nanopores without worsening PSi interferometer optical features.

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Based on previous theoretical and experimental results on the electrochemical etching of silicon in HF‐based aqueous electrolytes, it is shown for the first time that silicon microstructures of various shapes and silicon microsystems of high complexity can be effectively fabricated in any research lab with sub‐micrometer accuracy and high aspect ratio values (about 100). This is well beyond any up‐to‐date wet or dry microstructuring approach and is achieved using a wet etching, low‐cost technology: silicon electrochemical micromachining (ECM). Dynamic control of the etching anisotropy (from 1 to 0) as the electrochemical etching progresses allows the silicon dissolution to be switched in real‐time from the anisotropic to the isotropic regime and enables advanced silicon microstructuring to be achieved through the use of high‐aspect‐ratio functional and sacrificial structures, the former being functional to the microsystem operation and the latter being sacrificed for accurate microsystem fabrication. World‐wide dissemination of the ECM technology for silicon microstructuring is envisaged in the near future, due to its low cost and high flexibility, with high‐potential impact on, though not limited to, the broad field of microelectronics and microfabrication.